Use of electrically conductive materials for electrophysiology

ABSTRACT

Some embodiments of the present disclosure pertain to methods of improving electrical conduction across an impaired region of a tissue (e.g., myocardial tissue) by applying an electrically conductive material (e.g., carbon nanotube fibers) across the impaired region. The electrically conductive materials can become associated with non-impaired regions of the tissue on opposite sides of the impaired region by suturing. Such methods can also be utilized to treat or prevent cardiac arrhythmia in a subject (e.g., ventricular arrhythmia). Additional embodiments of the present disclosure pertain to electrical wirings that include carbon nanotubes, such as carbon nanotube fibers. Such electrical wirings can be used to transmit electrical signals to a tissue or sense electrical signals from the tissue. In some embodiments, the present disclosure also pertains to suture threads that include carbon nanotubes, such as carbon nanotube fibers.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/878,259, filed on Sep. 16, 2013; and U.S. Provisional PatentApplication No. 61/942,223, filed on Feb. 20, 2014. The entirety of eachof the aforementioned applications is incorporated herein by reference.

BACKGROUND

Current methods of treating cardiac arrhythmia suffer from numerouslimitations. Current methods of sensing electrical signals from cardiactissues and transmitting electrical signals to cardiac tissues alsosuffer from numerous limitations. Various embodiments of the presentdisclosure address the aforementioned limitations.

SUMMARY

In some embodiments, the present disclosure pertains to methods ofimproving electrical conduction across an impaired region of a tissue byapplying an electrically conductive material across the impaired region.In some embodiments, the tissue includes myocardial tissue. In someembodiments, the impaired region of the tissue includes, withoutlimitation, a scarred area, an ablated area, a bruised area, a cut area,a lesion, and combinations thereof.

In some embodiments, electrically conductive materials become associatedwith non-impaired regions of the tissue that are near the impairedregion of the tissue. In some embodiments, electrically conductivematerials become associated with non-impaired regions of the tissue thatare on opposite sides of the impaired region of the tissue. In someembodiments, the association occurs by suturing.

In some embodiments, the electrically conductive materials include,without limitation, fibers, wires, metal wires, foils, metal foils,conductive polymers, carbon nanotubes, materials made from carbonnanotubes, and combinations thereof. In some embodiments, theelectrically conductive materials include materials made from carbonnanotubes, such as carbon nanotube fibers.

In some embodiments, the electrically conductive materials of thepresent disclosure improve the electrical conduction across an impairedregion of a tissue by electrically connecting non-impaired regions ofthe tissue near the impaired region of the tissue. In some embodiments,the electrically conductive materials improve the electrical conductionacross an impaired region of a tissue by restoring or enhancingelectrical conduction across the impaired region of the tissue.

In some embodiments, the present disclosure pertains to methods oftreating or preventing cardiac arrhythmia in a subject by applying theelectrically conductive materials of the present disclosure across animpaired region of a tissue (e.g., myocardial tissue) in the subject. Insome embodiments, the subject is at risk of suffering from cardiacarrhythmia. In some embodiments, the subject is suffering from cardiacarrhythmia. In some embodiments, the cardiac arrhythmia to be treated isventricular arrhythmia.

In some embodiments, the present disclosure pertains to electricalwirings for sensing or transmitting electrical signals. In someembodiments, the electrical wiring includes carbon nanotubes. In someembodiments, the carbon nanotubes are in the form of carbon nanotubefibers. In some embodiments, the electrical wiring includes a conductiveelement and one or more points of attachment. In some embodiments, theelectrical wirings of the present disclosure are associated with anelectrical device, such as medical devices, pacemakers, defibrillators,electrocardiographs, and combinations thereof.

In some embodiments, the present disclosure pertains to methods oftransmitting electrical signals to a tissue by associating the tissuewith an electrical wiring of the present disclosure, and transmittingelectrical signals to the tissue through the electrical wiring. In someembodiments, the transmittal of electrical signals to the tissueincludes delivery of an electrical signal from an electrical deviceassociated with the electrical wiring (e.g., medical devices,pacemakers, defibrillators, and combinations thereof). In someembodiments where the tissue includes myocardial tissue in a subject,the methods of the present disclosure can be used for cardiacresynchronization or defibrillation in the subject.

In some embodiments, the present disclosure pertains to methods ofsensing electrical signals from a tissue by associating the tissue withan electrical wiring of the present disclosure, and sensing electricalsignals from the tissue through the electrical wiring. In someembodiments, the sensing of electrical signals from the tissue includessensing the electrical signals in an electrical device associated withthe electrical wiring (e.g., medical devices, pacemakers,defibrillators, electrocardiographs, and combinations thereof). In someembodiments where the tissue includes myocardial tissue in a subject,the sensing of electrical signals from the myocardial tissue includessensing of cardiac electrical activity.

In some embodiments, the present disclosure pertains to suture threadsthat include carbon nanotubes. In some embodiments, the carbon nanotubesin the suture threads include carbon nanotube fibers. In someembodiments, the suture threads consist essentially of carbon nanotubefibers. In some embodiments, the suture threads only consist of carbonnanotube fibers.

DESCRIPTION OF THE FIGURES

FIG. 1 provides schemes of methods of improving electrical conductionacross an impaired region of a tissue (FIG. 1A), methods of treating orpreventing cardiac arrhythmia in a subject (FIG. 1C), methods of sensingelectrical signals from a tissue by associating the tissue with anelectrical wiring that includes carbon nanotubes (FIG. 1E), and methodsof sensing electrical signals from a tissue by associating the tissuewith the electrical wiring (FIG. 1F). A depiction of a system forimproving electrical conduction across an impaired region of a tissue isalso shown (FIG. 1B). A system for sensing or transmitting electricalsignals is also shown (FIG. 1D).

FIG. 2 shows experimental setups and data relating to the use of acarbon nanotube fiber (CNTf or CNT fibers) as an electrode configurationfor restoring electrical conduction in cardiac tissues. FIG. 2A is aphotograph of the left ventricle (LV) of a heart with a radiofrequency(RF) scar caused by RF ablation. A CNT fiber has been placed across theRF scar. FIG. 2B is a photograph of the CNT fiber. FIG. 2C is a diagramshowing the locations of decapolar catheters and the CNT fiber pacingleads on the ventricle of a heart prior to RF ablation. FIG. 2D is adiagram showing the locations of decapolar catheters and the CNT fiberpacing leads on the ventricle of a heart after RF ablation.

FIG. 3 shows that CNT fibers improve conduction time in areas ofmyocardial conduction block (i.e., areas of RF lesion). Histograms ofconduction times at a pacing frequency of 150 beats per minute (BPM)(i.e., CL 400 ms) in the locations proximal (11 o'clock) (FIG. 3A) anddistal (2 o'clock) (FIG. 3B) to CNT fiber implants are shown. When theCNT fiber was implanted across the RF lesion, a significant improvementon conduction time compared to RF lesion and silk condition was measuredat the 11 o'clock position (FIG. 3A), but not at the 2 o'clock position(FIG. 3B). A two way ANOVA test was used for effects of conditionF((1.1727, 27.634)=173.484, P<0.0005) and of locations (F(1.1844,29.500)=6.673, P<0.005). Post-hoc pairwise comparisons with Bonferronicorrection was used to compare the different conditions. Values arepresented as mean±S.E.M. ***p<0.001, ns=not significant.

FIG. 4 shows conduction intervals measured across the entire RF ablatedLV area shown in FIG. 2A. FIG. 4A is a map of the locations in theexperimental area where the conduction velocity was measured. FIGS. 4B-Eshow the average conduction intervals measured by the 4 arrays ofdecapolar catheters in three animal experiments. Concentric circlesrepresent time (in ms), whereas radial positions represent the locationof the channel where intervals were measured. Brown areas in FIGS. 4C-Erepresent the RF lesion. Yellow circles in FIGS. 4D-E represent thelocations where CNT fibers and silk sutures were implanted,respectively.

FIG. 5 shows local activation time maps of epicardial tissue. The imagein FIG. 5B shows significant slowing of myocardial conduction across theC-shaped scar created by RF ablation (red dots pointed by red arrows)when compared to the baseline condition (FIG. 5A). FIG. 5C shows thatmyocardial conduction improved only in the area where CNT fibers weresutured across the RF lesion (yellow dots pointed by yellow arrows).Activation time and propagation maps are rotated by ˜90 degrees comparedto the orientation shown in FIG. 2A for ease of visualization.

FIG. 6 shows improved sinus conduction with CNT fibers across an RFlesion in the right atrium. FIG. 6A shows the experimental setup. FIG.6B shows conduction time measured at the channels nearest to the CNTfibers. The results indicate that CNT fibers can transduce myocardialaction potentials across an area of slow conduction without needingexternal pacing. Bars show mean±S.E.M.

FIG. 7 shows data demonstrating myocardial pacing and sensing with CNTfibers. FIG. 7A shows data validating myocardial pacing at 150 BPM(i.e., CL 400 ms) with CNT fibers. FIG. 7B shows data validating thesensing of myocardial potential at sinus rhythm with CNT fibers and themost proximal standard epicardial electrode.

DETAILED DESCRIPTION

It is to be understood that both the foregoing general description andthe following detailed description are illustrative and explanatory, andare not restrictive of the subject matter, as claimed. In thisapplication, the use of the singular includes the plural, the word “a”or “an” means “at least one”, and the use of “or” means “and/or”, unlessspecifically stated otherwise. Furthermore, the use of the term“including”, as well as other forms, such as “includes” and “included”,is not limiting. Also, terms such as “element” or “component” encompassboth elements or components comprising one unit and elements orcomponents that include more than one unit unless specifically statedotherwise.

The section headings used herein are for organizational purposes and arenot to be construed as limiting the subject matter described. Alldocuments, or portions of documents, cited in this application,including, but not limited to, patents, patent applications, articles,books, and treatises, are hereby expressly incorporated herein byreference in their entirety for any purpose. In the event that one ormore of the incorporated literature and similar materials defines a termin a manner that contradicts the definition of that term in thisapplication, this application controls.

Disruption in normal electrical cardiac conduction leads to slowedconduction zones (SZC's). These SZC's provide the substrate for numerousforms of cardiac arrhythmia, mainly those utilizing re-entry as theirprimary mechanism. Existing treatment methods cannot restore normalconductive function to these SZC's. Several treatment methods forcardiac arrhythmia work by modifying the conduction speed of the rest ofthe myocardial tissue to counteract the effects of SZC's. For instance,anti-arrhythmic treatment methods include administration of drugs thatmodify the speed of conduction in myocardial tissue. Such treatmentmethods are also conducted by controlled and localized deactivation ofsome areas of the heart (i.e., catheter ablation). Anti-arrhythmictherapies have also included ablation of impaired areas. However,ablation irreversibly causes permanent scarring of the heart withoutaddressing the mechanism of reentrant arrhythmias, such as conductionslowing.

Furthermore, the aforementioned anti-arrhythmic therapies demonstratevaried and limited efficacies in different patient populations. Suchanti-arrhythmic therapies may also involve further slowing orelimination of conduction, either by increasing the cardiac electricalrefractory periods or cardiac ablation.

Current methods of sensing electrical signals from cardiac tissues andtransmitting electrical signals to cardiac tissues also suffer fromnumerous limitations. For instance, current implantable electrodes forpacemakers are usually millimeter-size metal leads. Because theseelectrodes are bulky and invasive, the process of insertion and removalcan cause extensive damage to nearby tissue. The current metalelectrodes are also subject to degradation and bending fatigue.

Various embodiments of the present disclosure address the aforementionedlimitations. In some embodiments, the present disclosure pertains tomethods of improving electrical conduction across an impaired region ofa tissue. In some embodiments, the present disclosure pertains tomethods of treating or preventing cardiac arrhythmia in a subject. Insome embodiments, the present disclosure pertains to methods oftransmitting electrical signals to a tissue by associating the tissuewith an electrical wiring that includes carbon nanotubes. In someembodiments, the present disclosure pertains to methods of sensingelectrical signals from a tissue by associating the tissue with anelectrical wiring that includes carbon nanotubes. In some embodiments,the present disclosure pertains to carbon nanotube-containing electricalwirings for sensing or transmitting electrical signals from a tissue. Insome embodiments, the present disclosure pertains to suture threads thatinclude carbon nanotubes.

Improvement of Electrical Conduction in Tissues

In some embodiments, the present disclosure pertains to methods ofimproving electrical conduction across an impaired region of a tissue.In some embodiments illustrated in FIG. 1A, such methods can includeapplying an electrically conductive material across the impaired regionof the tissue (step 10). In some embodiments, the applying results inthe association of the electrically conductive material withnon-impaired regions of the tissue near the impaired region of thetissue (step 12). In some embodiments, the applying also results in theelectrical connection of the non-impaired regions of the tissue near theimpaired region of the tissue (step 14). Such methods result in theimprovement of electrical conduction across the impaired region of thetissue (step 16).

An example of a system for improving electrical conduction across animpaired region of a tissue is shown in FIG. 1B. In this depiction,tissue 30 contains impaired region 32 between non-impaired regions 34and 36. Electrically conductive material 38 is electrically connected tonon-impaired regions 34 and 36 through sutures 40. This electricalconnection improves electrical conduction across impaired region 32.

As set forth in more detail herein, methods of improving electricalconduction across an impaired region of a tissue may be applied tovarious tissues with various types of impaired regions. Moreover,various methods may be utilized to apply various types of electricallyconductive materials to impaired regions of tissues. Furthermore, theelectrical conduction of tissues across an impaired region of a tissuemay be improved in various ways.

Tissues

The methods of the present disclosure may be utilized to improveelectrical conduction in various tissues. In some embodiments, thetissue includes, without limitation, nerve tissue, muscle tissue,myocardial tissue, and combinations thereof. In some embodiments, thetissue includes a single tissue type. In some embodiments, the tissueincludes multiple tissue types.

In some embodiments, the tissue includes myocardial tissue. In someembodiments, the myocardial tissue includes ventricular tissue. In someembodiments, the myocardial tissue includes atrial tissue.

Impaired Regions of Tissues

The methods of the present disclosure may be utilized to improveelectrical conduction across various impaired regions of tissues. Insome embodiments, the impaired regions of tissues include at least oneof a scarred area, an ablated area, a bruised area, a cut area, alesion, and combinations thereof.

The impaired regions of tissues may have various shapes. For instance,in some embodiments, the impaired regions of tissues can be in the formof squares, circles, ovals, and combinations of such shapes.

The impaired regions of tissues may also be derived from various tissuetypes. For instance, in some embodiments, the impaired regions oftissues include a single tissue type. In some embodiments, the impairedregions of tissues include multiple tissue types. In some embodiments,the multiple tissue types can include nerve tissue and muscle tissue.

In some embodiments, the impaired regions of tissues include impairedmyocardial tissue. In some embodiments, the impaired regions of tissuesinclude impaired ventricular tissue, such as impaired left ventriculartissue. In some embodiments, the impaired regions of tissues includeimpaired atrial tissue, such as impaired right atrial tissue.

Impaired regions of tissues may exhibit various properties. Forinstance, in some embodiments, the impaired regions of tissues exhibitblocked or reduced electrical conduction. In some embodiments, theimpaired regions of tissues exhibit blocked or reduced passage of adepolarization wave. In some embodiments, the impaired regions oftissues exhibit blocked or reduced transmission of ion voltages fromcell to cell. In some embodiments, the impaired regions of tissuesrepresent a slowed conduction zone (SZC). In some embodiments, theimpaired regions of tissues exhibit blocked or impaired actionpotentials within cells. In some embodiments, the impaired regions oftissues are electrically inactive.

In some embodiments, the impaired regions of tissues exhibit blocked orreduced contraction. For instance, in some embodiments, the impairedregions of tissues contract at a delayed time relative to other regionsof the tissue.

Application of Electrically Conductive Materials to Tissues

Various methods may be utilized to apply an electrically conductivematerial across an impaired region of a tissue. In some embodiments, theapplying includes associating the electrically conductive material withnon-impaired regions of the tissue near the impaired region of thetissue. In some embodiments, the non-impaired regions of the tissue areon opposite sides of an impaired region of the tissue (e.g.,non-impaired regions 34 and 36 in FIG. 1B).

In some embodiments, non-impaired regions of tissues exhibit normalelectrical conduction. For instance, in some embodiments, thenon-impaired regions of tissues exhibit normal passage of adepolarization wave. In some embodiments, the non-impaired regions oftissues exhibit normal transmission of ion voltages from cell to cell.In some embodiments, the non-impaired regions of tissues exhibit normalaction potentials within cells. In some embodiments, the non-impairedregions of tissues are electrically active. In some embodiments, thenon-impaired regions of tissues exhibit normal contraction.

In some embodiments, the associating of electrically conductivematerials with non-impaired regions of the tissue near an impairedregion of the tissue results in the formation of a bridge across theimpaired region of the tissue (e.g., electrically conductive material 38in FIG. 1B). In some embodiments, the associating of electricallyconductive materials with non-impaired regions of the tissue near animpaired region of the tissue results in the formation of an electricalconnection across the impaired region of the tissue.

In some embodiments, the associating of electrically conductivematerials with non-impaired regions of the tissue near an impairedregion of the tissue occurs by implanting the electrically conductivematerials into the non-impaired regions of the tissue. In someembodiments, the associating of electrically conductive materials withnon-impaired regions of the tissue near an impaired region of the tissueoccurs by suturing the electrically conductive materials into thenon-impaired regions of the tissue (e.g., sutures 40 in FIG. 1B). Insome embodiments, the suturing includes, without limitation, directsuturing, external suturing on the tissue, internal suturing within thetissue, and combinations thereof. In some embodiments, the electricallyconductive materials may serve as the sutures.

In some embodiments, the associating of electrically conductivematerials with non-impaired regions of the tissue near an impairedregion of the tissue occurs by placing the electrically conductivematerial over a surface of the impaired region of the tissue. In someembodiments, the placement can include covering of the impaired regionof the tissue, patching of the impaired region of the tissue, implantingthe electrically conductive material over or through the impaired regionof the tissue, and combinations thereof.

Electrically Conductive Materials

The methods of the present disclosure may utilize various types ofelectrically conductive materials. In some embodiments, suitableelectrically conductive materials include materials with sufficientlylow resistivity. In some embodiments, suitable electrically conductivematerials include materials with sufficiently low contact impedance witha tissue. In some embodiments, suitable electrically conductivematerials include materials that are able to effectively transferelectric current between regions of a tissue (e.g., transmission ofmyocardial action potentials between cells). In some embodiments,suitable electrically conductive materials include materials that allownatural conduction signals to be transmitted in such a way thatre-entrant currents are avoided. In some embodiments, suitableelectrically conductive materials include materials with sufficientflexibility to bend along with tissue contraction without damaging orputting significant pressure on nearby tissues. In some embodiments,suitable electrically conductive materials include materials withsufficient resistance to flex fatigue to undergo such bending for atleast 10 million cycles without degradation or fracture.

In some embodiments, suitable electrically conductive materials includematerials with a resistivity that ranges from about 100 μΩ to cm toabout 1 μΩ cm. In some embodiments, suitable electrically conductivematerials include materials that have a contact impedance with a tissuethat ranges from about 5 MOhm μm² to about 50 MOhm μm².

In some embodiments, suitable electrically conductive materials include,without limitation, fibers, wires, metal wires, foils, metal foils,conductive polymers, carbon nanotubes, materials made from carbonnanotubes, and combinations thereof. In some embodiments, theelectrically conductive material is coated with an adhesive material. Insome embodiments, the adhesive material includes, without limitation,polyethylene glycol (PEG), chitosan, sucrose solutions, gelatin, andcombinations thereof. In some embodiments, the adhesive material isbiodegradable. In some embodiments, the electrically conductive materialis uncoated.

The electrically conductive materials of the present disclosure may havevarious sizes. For instance, in some embodiments, the electricallyconductive materials of the present disclosure include diameters thatrange from about 5 μm to about 5 mm. In some embodiments, theelectrically conductive materials of the present disclosure includediameters that range from about 500 μm to about 1 mm. In someembodiments, the electrically conductive materials of the presentdisclosure include diameters that range from about 5 μm to about 500 μm.In some embodiments, the electrically conductive materials of thepresent disclosure include diameters that range from about 8 μm to about200 μm.

The electrically conductive materials of the present disclosure may alsohave various shapes. For instance, in some embodiments, the electricallyconductive materials of the present disclosure are in the form offibers, films, patches, filaments, sheets, mesh, sutures, networksthereof, and combinations thereof. In some embodiments, the electricallyconductive materials of the present disclosure are in the form of a meshof network of filaments woven together. In some embodiments, theelectrically conductive materials of the present disclosure are in theform of a woven network of filaments. In some embodiments, theelectrically conductive materials of the present disclosure are in theform of a shape memory filament. In some embodiments, the electricallyconductive materials of the present disclosure are in the form of thinconductive films, such as thin conductive carbon nanotube films. In someembodiments, the electrically conductive materials of the presentdisclosure are in the form of sutures, such as closed loops of sutures.In some embodiments, the electrically conductive materials of thepresent disclosure are in the form of wires. In some embodiments, theelectrically conductive materials of the present disclosure are in theform of interwoven wires.

In some embodiments, the electrically conductive materials of thepresent disclosure include fibers. In some embodiments, the fibersinclude bundles of fibers. In some embodiments, the fibers includeinterwoven fibers. In some embodiments, the fibers include individualfibers.

In some embodiments, the electrically conductive materials of thepresent disclosure include carbon nanotubes. In some embodiments, thecarbon nanotubes include, without limitation, single-walled carbonnanotubes, ultra-short single-walled carbon nanotubes, multi-walledcarbon nanotubes, and combinations thereof.

In some embodiments, the electrically conductive materials of thepresent disclosure include carbon nanotube fibers. In some embodiments,the electrically conductive materials of the present disclosure onlyinclude carbon nanotube fibers. In some embodiments, the electricallyconductive materials of the present disclosure consist essentially ofcarbon nanotube fibers. In some embodiments, the carbon nanotube fibersof the present disclosure include the carbon nanotube fibers disclosedin U.S. Pat. No. 7,125,502. In some embodiments, the carbon nanotubefibers of the present disclosure include the carbon nanotube fibersdisclosed in U.S. patent application Ser. No. 12/740,529.

The carbon nanotube fibers of the present disclosure may be fabricatedby various methods. For instance, in some embodiments, carbon nanotubefibers of the present disclosure are fabricated by spinning highconcentration carbon nanotube solutions out of an orifice and into acoagulant bath by a previously patented process. See, e.g., U.S. Pat.No. 7,125,502. Also see U.S. patent application Ser. No. 12/740,529. Thecarbon nanotube fibers (single or in bundles) can then be used tofabricate electrically conductive materials with a desired morphology.Moreover, the carbon nanotube fibers can be post-processed andcustomized for a specific use (e.g., coating with insulating polymers).In some embodiments, the carbon nanotube fibers of the presentdisclosure can also be manufactured with other types of carbon nanotubefibers, such as carbon nanotube fibers spun by direct spinning.

In some embodiments, the carbon nanotube fibers of the presentdisclosure include, without limitation, individual carbon nanotubesfibers, interwoven carbon nanotube fibers, coated carbon nanotubefibers, uncoated carbon nanotube fibers, aligned carbon nanotube fibers,bundles of carbon nanotube fibers, and combinations thereof.

In some embodiments, the electrically conductive materials of thepresent disclosure include single-walled carbon nanotube fibers. In someembodiments, the electrically conductive materials of the presentdisclosure include fibers of aligned single-walled carbon nanotubes.

In some embodiments, the electrically conductive materials of thepresent disclosure include multi-walled carbon nanotube fibers. In someembodiments, the electrically conductive materials of the presentdisclosure include fibers of aligned multi-walled carbon nanotubes.

In some embodiments, the carbon nanotube fibers of the presentdisclosure include diameters that range from about 5 μm to about 5 mm.In some embodiments, the carbon nanotube fibers of the presentdisclosure include diameters that range from about 500 μm to about 1 mm.In some embodiments, the carbon nanotube fibers of the presentdisclosure include diameters that range from about 5 μm to about 500 μm.In some embodiments, the carbon nanotube fibers of the presentdisclosure include diameters that range from about 8 μm to about 200 μm.

Improvement of Electrical Conduction in Tissues

The methods of the present disclosure can improve electrical conductionacross an impaired region of a tissue by various mechanisms. Forinstance, in some embodiments, an electrically conductive material canimprove the electrical conduction across an impaired region of a tissueby electrically connecting non-impaired regions of the tissue near theimpaired region of the tissue. In some embodiments, the electricallyconductive materials of the present disclosure electrically connect oneside of the impaired region of a tissue to another side of the impairedregion of the tissue. In some embodiments, the electrical connection islongitudinal.

In some embodiments, the electrical connection of non-impaired regionsof the tissue near the impaired region of the tissue results intransmittal of electrical currents across an impaired region of atissue. In some embodiments, the electrical connection results intransduction of action potentials across an impaired region of a tissue(e.g., transduction of myocardial action potentials across impairedmyocardial tissues).

In some embodiments, the electrical connection results in thetransmittal of ion-regulated voltage signals across an impaired regionof a tissue. In some embodiments, the transmitted voltage signals may beassociated with depolarization. In some embodiments, a wave ofdepolarization moving through a tissue would reach the electricallyconductive material and result in a voltage drop across the conductivematerial (due to the difference in electric potential between“depolarized” tissue and “polarized” tissue in contact with oppositesides of the electrically conductive material). This voltage drop cansubsequently initiate depolarization of the tissue both within theimpaired region and non-impaired regions of the tissue, thereby allowingthe depolarization wave to proceed through the impaired region of thetissue with little or no change in speed relative to its passage inother regions of the tissue. In some embodiments, the transmittedvoltage signals may be associated with depolarization in a myocardialtissue in connection with a heartbeat.

In some embodiments, the electrically conductive material improveselectrical conduction across an impaired region of a tissue by restoringelectrical conduction across an impaired region of a tissue. In someembodiments, the restoration of electrical conduction includesnormalization of electrical conduction across an impaired region of atissue. In some embodiments, the restoration of electrical conductionincludes restoration of normal electrical conduction pathways across animpaired region of a tissue. In some embodiments, the restoration ofelectrical conduction includes restoration of normal electricalconduction velocities. In some embodiments, the restoration ofelectrical conduction includes restoration of synchronized contractionof an impaired region of a tissue.

In some embodiments, the electrically conductive material improves theelectrical conduction across an impaired region of a tissue by enhancingelectrical conduction across the impaired region of the tissue. In someembodiments, electrical conduction is enhanced by about 10% to about95%. In some embodiments, electrical conduction is enhanced by about 10%to about 50%. In some embodiments, electrical conduction is enhanced byabout 10% to about 25%. In some embodiments, electrical conduction isenhanced by about 15% to about 20%.

In some embodiments, the electrically conductive material improves theelectrical conduction across an impaired region of a tissue bydecreasing electrical current conduction time across the impaired regionof the tissue. In some embodiments, electrical conduction time isreduced by about 10% to about 50%. In some embodiments, electricalconduction time is reduced by about 10% to about 25%. In someembodiments, electrical conduction time is reduced by about 15% to about20%. In some embodiments, electrical conduction time is reduced by about1 ms to about 20 ms. In some embodiments, electrical conduction time isreduced by about 2 ms to about 10 ms.

Treatment or Prevention of Cardiac Arrhythmia

In some embodiments, the present disclosure pertains to methods oftreating or preventing cardiac arrhythmia in a subject. In someembodiments, the aforementioned methods of improving electricalconduction across an impaired region of a tissue may be utilized totreat or prevent cardiac arrhythmia in a subject. In some embodimentsillustrated in FIG. 1C, such methods can include applying anelectrically conductive material across an impaired region of a tissuein a subject (step 20). In some embodiments, the applying results in theassociation of the electrically conductive material with non-impairedregions of the tissue near the impaired region of the tissue in thesubject (step 22). In some embodiments, the applying also results in theelectrical connection of the non-impaired regions of the tissue near theimpaired region of the tissue in the subject (step 24). In someembodiments, the applying also results in the improvement of electricalconduction across the impaired region of the tissue in the subject (step26). Such methods result in the treatment or prevention of cardiacarrhythmia in a subject (step 28).

As set forth previously, the methods of the present disclosure may beapplied to various tissues with various types of impaired regions. Forinstance, in some embodiments, the tissue includes myocardial tissue,such as ventricular tissue or atrial tissue. In some embodiments, theimpaired regions of tissues include impaired myocardial tissue, such asimpaired ventricular tissue (e.g., impaired left ventricular tissue) orimpaired atrial tissue (e.g., impaired right atrial tissue).

As also set forth previously, various methods may be utilized to applyvarious types of electrically conductive materials across impairedregions of tissues. As also set forth previously, the applying canresult in the association of electrically conductive materials withnon-impaired regions of a tissue near the impaired region of the tissuein various manners. As also set forth previously, the applying canresult in the electrical connection of non-impaired regions of a tissuenear the impaired region of the tissue in the subject in variousmanners. Furthermore, the electrical conduction of tissues may beimproved in various ways that were described previously. As set forth inmore detail herein, the treatment or prevention methods of the presentdisclosure may be utilized to treat or prevent various types of cardiacarrhythmias in various subjects.

Subjects

The treatment or prevention methods of the present disclosure may beapplied to various subjects. In some embodiments, the subject is at riskof suffering from cardiac arrhythmia. In some embodiments, the subjectis suffering from cardiac arrhythmia.

In some embodiments, the subject may be a non-human animal, such asmice, rats, other rodents, or larger mammals, such as dogs, monkeys,pigs, sheep, cattle and horses. In some embodiments, the subject may bea mammal, such as a sheep.

In some embodiments, the subject is a human being. In some embodiments,the subject is a human being at risk of suffering from cardiacarrhythmia. In some embodiments, the subject is a human being sufferingfrom cardiac arrhythmia.

Cardiac Arrhythmias

In some embodiments, the methods of the present disclosure are utilizedto treat cardiac arrhythmia. In some embodiments, the methods of thepresent disclosure are utilized to prevent cardiac arrhythmia. In someembodiments, the methods of the present disclosure are utilized to treatand prevent cardiac arrhythmia.

The methods of the present disclosure may be utilized to treat orprevent various types of cardiac arrhythmias. For instance, in someembodiments, the cardiac arrhythmia is ventricular arrhythmia. In someembodiments, the cardiac arrhythmia is atrial arrhythmia.

The methods of the present disclosure can be utilized to treat orprevent cardiac arrhythmia by various mechanisms. For instance, in someembodiments, cardiac arrhythmia is treated or prevented by normalizingthe heart rhythm of a subject. In some embodiments, cardiac arrhythmiais treated or prevented by improving the heart rhythm of a subject.

In some embodiments, the heart's rhythm is normalized by improvingconduction in zones of slowed or diseased myocardial conduction. In someembodiments, this improved conduction may have an anti-arrhythmic effectby increasing the “wavelength” of the re-entrant arrhythmic circuit,thereby improving conduction velocity and increasing the “wavelength”(i.e., a product of conduction velocity and refractory period). It isenvisioned that any maneuver that increases the wavelength renders agreater tissue requirement for sustaining arrhythmia, thus rendering itssustenance less likely.

Electrical Wirings

In some embodiments, the present disclosure pertains to an electricalwiring. In some embodiments, the electrical wiring can be utilized tosense electrical signals from a tissue or transmit electrical signals toa tissue. In some embodiments, the electrical wiring includes carbonnanotubes. In some embodiments, the electrical wirings of the presentdisclosure consist essentially of carbon nanotubes. In some embodiments,the electrical wirings of the present disclosure only contain carbonnanotubes.

Carbon Nanotubes

The electrical wirings of the present disclosure may include varioustypes of carbon nanotubes. For instance, in some embodiments, the carbonnanotubes can include, without limitation, single-walled carbonnanotubes, ultra-short single-walled carbon nanotubes, multi-walledcarbon nanotubes, and combinations thereof.

In some embodiments, the carbon nanotubes of the electrical wirings ofthe present disclosure are coated with an adhesive material. In someembodiments, the adhesive material includes, without limitation,polyethylene glycol (PEG), chitosan, sucrose solutions, gelatin, andcombinations thereof. In some embodiments, the adhesive material isbiodegradable. In some embodiments, the carbon nanotubes of theelectrical wirings of the present disclosure are uncoated.

In some embodiments, the carbon nanotubes of the electrical wirings ofthe present disclosure are in the form of carbon nanotube fibers (asdescribed previously). In some embodiments, the electrical wirings ofthe present disclosure consist essentially of carbon nanotube fibers. Insome embodiments, the electrical wirings of the present disclosure onlycontain carbon nanotube fibers. In some embodiments, the carbon nanotubefibers include, without limitation, single-walled carbon nanotubefibers, multi-walled carbon nanotube fibers, aligned carbon nanotubesfibers, and combinations thereof.

In some embodiments, the carbon nanotube fibers of the electricalwirings of the present disclosure include diameters that range fromabout 5 μm to about 5 mm. In some embodiments, the carbon nanotubefibers include diameters that range from about 500 μm to about 1 mm. Insome embodiments, the carbon nanotube fibers include diameters thatrange from about 5 μm to about 500 μm. In some embodiments, the carbonnanotube fibers include diameters that range from about 8 μm to about200 μm.

Electrical Wiring Configurations

The electrical wirings of the present disclosure can have variousshapes. For instance, in some embodiments, the electrical wirings of thepresent disclosure include a conductive element and a point ofattachment. In some embodiments, the conductive element is in the formof a wire or fiber. In some embodiments, the point of attachment is inthe form of an adhesive patch or an electrode. In some embodiments, thepoint of attachment is in the form of an electrode. In some embodiments,the electrical wiring includes a plurality of points of attachment.

In some embodiments, the conductive element includes carbon nanotubes,such as carbon nanotube fibers. In some embodiments, the point ofattachment includes carbon nanotubes, such as carbon nanotube fibers. Insome embodiments, the conductive element and the point of attachmentboth include carbon nanotubes, such as carbon nanotube fibers.

In some embodiments, the electrical wirings of the present disclosuremay be associated with an electrical device. In some embodiments, theelectrical device includes, without limitation, medical devices,pacemakers, defibrillators, electrocardiographs, and combinationsthereof. In some embodiments, the electrical device is a pacemaker. Insome embodiments, the electrical device is a defibrillator. In someembodiments, the electrical device is an implantable cardioverterdefibrillator (ICD).

An example of an electrical wiring associated with an electrical deviceis illustrated in FIG. 1D. In this example, electrical wiring 10includes conductive element 12 and point of attachment 14. Conductiveelement 12 in this example can be in the form of a fiber, such as acarbon nanotube fiber. Likewise, point of attachment 14 can be in theform of an electrode, such as an electrode containing carbon nanotubes.Conductive element 12 is associated with electrical device 20 whilepoint of attachment 14 is associated with subject 16.

As set forth in more detail herein, the electrical wirings of thepresent disclosure may be utilized to transmit electrical signals tovarious tissues. As also set forth in more detail herein, the electricalwirings of the present disclosure may be utilized to sense variouselectrical signals from various tissues.

Methods of Transmitting Electrical Signals to a Tissue

In some embodiments, the present disclosure pertains to methods oftransmitting electrical signals to a tissue. In some embodimentsillustrated in FIG. 1E, the method involves associating the tissue withan electrical wiring that includes carbon nanotubes (step 30). In someembodiments, the method also involves transmitting electrical signals tothe tissue through the electrical wiring (step 32). In some embodiments,such methods may be utilized for cardiac defibrillation (step 34) orcardiac resynchronization (step 36).

The transmittal methods of the present disclosure may utilize varioustypes of electrical wirings. Suitable electrical wirings were disclosedpreviously. As set forth in more detail herein, various methods may beutilized to associate various types of electrical wirings with varioustypes of tissues. Moreover, various types of electrical signals may betransmitted to tissues from various electrical devices.

Tissues

The electrical wirings of the present disclosure may be associated withvarious types of tissues. In some embodiments, the tissue includes,without limitation, nerve tissue, muscle tissue, myocardial tissue, andcombinations thereof. In some embodiments, the tissue includes a singletissue type. In some embodiments, the tissue includes multiple tissuetypes. In some embodiments, the tissue includes myocardial tissue. Insome embodiments, the myocardial tissue includes ventricular tissue oratrial tissue.

In some embodiments, the tissue is an isolated tissue. In someembodiments, the tissue is part of a subject. In some embodiments, thesubject is at risk of suffering from cardiac arrhythmia. In someembodiments, the subject is suffering from cardiac arrhythmia.

In some embodiments, the subject may be a non-human animal, such asmice, rats, other rodents, or larger mammals, such as dogs, monkeys,pigs, sheep, cattle and horses. In some embodiments, the subject may bea mammal, such as a sheep.

In some embodiments, the subject is a human being. In some embodiments,the subject is a human being at risk of suffering from cardiacarrhythmia. In some embodiments, the subject is a human being sufferingfrom cardiac arrhythmia.

Association of Tissues with Electrical Wirings

Various methods may be utilized to associate tissues with electricalwirings. For instance, in some embodiments, the associating includesimplanting the electrical wiring into the tissue. In some embodiments,the associating includes suturing the electrical wiring into the tissue.In some embodiments, the associating includes adhering the electricalwiring to or nearby the tissue. In some embodiments, the associatingforms an electrical interface between the electrical wiring and thetissue.

In some embodiments, the associating includes directly associating theelectrical wiring with a tissue. In some embodiments, the associatingincludes indirectly associating the electrical wiring with a tissue. Forinstance, in some embodiments, the associating includes indirectlyassociating an electrical wiring with myocardial tissue by placing apoint of attachment of the electrical wiring on the skin of a subjectnear the myocardial tissue (See, e.g., FIG. 1D).

Transmittal of Electrical Signals

Various methods may also be utilized to transmit electrical signals to atissue. For instance, in some embodiments, the transmittal includesdelivery of an electrical signal from an electrical device associatedwith an electrical wiring. In some embodiments, the electrical deviceincludes, without limitation, medical devices, pacemakers,defibrillators, and combinations thereof.

Applications

The aforementioned methods of transmitting electrical signals to atissue can be used for various purposes. For instance, in someembodiments where the tissue includes myocardial tissue in a subject,the methods of the present disclosure can be used for cardiacresynchronization in the subject. In some embodiments, the transmittalof electrical signals to the myocardial tissue includes delivery of aresynchronization shock from an electrical device (e.g., a pacemaker)associated with an electrical wiring. In some embodiments, thetransmittal of electrical signals can be utilized for left ventricularpacing, control of heart beat rate at desired frequencies, andcombinations thereof.

In some embodiments where the tissue includes myocardial tissue in asubject, the methods of the present disclosure can be used fordefibrillation in the subject. For instance, in some embodiments, themethods of the present disclosure can be used for delivery of adefibrillation shock from an electrical device (e.g., a defibrillator)associated with an electrical wiring. In some embodiments, thetransmittal of electrical signals can be used to treat cardiacdysrhythmias, ventricular fibrillation, pulseless ventriculartachycardia, and combinations thereof.

A Method of Sensing Electrical Signals from a Tissue

In some embodiments, the present disclosure pertains to methods ofsensing electrical signals from a tissue. In some embodimentsillustrated in FIG. 1F, the method involves associating the tissue withan electrical wiring that includes carbon nanotubes (step 40). In someembodiments, the method also involves sensing electrical signals fromthe tissue through the electrical wiring (step 42). In some embodiments,such methods may be utilized for electrocardiography (step 44).

The sensing methods of the present disclosure may utilize various typesof electrical wirings. Suitable electrical wirings were disclosedpreviously. As also set forth previously, various methods may beutilized to associate various types of electrical wirings with varioustypes of tissues in various subjects. Moreover, as set forth in moredetail herein, various electrical signals may be sensed from tissues byvarious electrical devices.

For instance, in some embodiments, the sensing of electrical signalsfrom a tissue includes sensing electrical signals in an electricaldevice associated with an electrical wiring. In some embodiments, theelectrical device includes, without limitation, medical devices,pacemakers, defibrillators, electrocardiographs, and combinationsthereof. In some embodiments where a tissue includes myocardial tissuein a subject, the sensing of electrical signals from the myocardialtissue in the subject includes sensing of cardiac electrical activity.In some embodiments, the sensing can be utilized forelectrocardiography.

Suture Threads

In some embodiments, the present disclosure pertains to suture threadsthat include carbon nanotubes. In some embodiments, the suture threadsof the present disclosure consist essentially of carbon nanotubes. Insome embodiments, the suture threads of the present disclosure onlycontain carbon nanotubes.

The suture threads of the present disclosure may include various typesof carbon nanotubes. For instance, in some embodiments, the carbonnanotubes can include, without limitation, single-walled carbonnanotubes, ultra-short single-walled carbon nanotubes, multi-walledcarbon nanotubes, and combinations thereof.

In some embodiments, the carbon nanotubes of the suture threads of thepresent disclosure are in the form of carbon nanotube fibers. In someembodiments, the carbon nanotube fibers include, without limitation,single-walled carbon nanotube fibers, multi-walled carbon nanotubefibers, aligned carbon nanotubes fibers, and combinations thereof. Insome embodiments, the suture threads of the present disclosure consistessentially of carbon nanotube fibers. In some embodiments, the suturethreads of the present disclosure only contain carbon nanotube fibers.

The suture threads of the present disclosure can have various diameters.For instance, in some embodiments, suture threads of the presentdisclosure include diameters that range from about 5 μm to about 5 mm.In some embodiments, the suture threads of the present disclosureinclude diameters that range from about 500 μm to about 1 mm. In someembodiments, the suture threads of the present disclosure includediameters that range from about 5 μm to about 500 μm. In someembodiments, the suture threads of the present disclosure includediameters that range from about 8 μm to about 200 μm.

The suture threads of the present disclosure can also have variouslengths. For instance, in some embodiments, the suture threads of thepresent disclosure have lengths that range from about 1 m to about 1 mm.In some embodiments, the suture threads of the present disclosure havelengths that range from about 10 cm to about 100 mm. In someembodiments, the suture threads of the present disclosure have lengthsthat range from about 1 cm to about 1 mm.

Advantages

Various embodiments of the present disclosure provide numerousadvantages and applications. For instance, because of their combinationof electrical conductivity, mechanical strength, flexibility, fatigueresistance, and low contact impedance, the carbon nanotube fibers of thepresent disclosure can provide optimal materials for electrical wirings(e.g., functional electrodes). For instance, in some embodiments, thecarbon nanotube fibers of the present disclosure can provide electrodesfor pacing and sensing heart electric activity. In some embodiments, thecarbon nanotube fibers of the present disclosure can also be used torestore cardiac conduction through electrically inactive cardiac scar.In the above applications, the carbon nanotube fibers of the presentdisclosure can be directly sutured on the myocardial tissue, either inexternal or intracardiac locations.

In some embodiments, the high electric conductivity carbon nanotubefibers of the present disclosure can be connected to any device forheart sensing/pacing, thereby enabling the bidirectional transmission ofhigh quality electric signals. Moreover, due to their small, flexible,strong and electrically stable properties, the carbon nanotube fibers ofthe present disclosure can be sutured on the heart with a significantimprovement of electrode/tissue contact, precision of sensing/pacing,and minimization of mechanical trauma to the tissue due to electrodeinsertion and motion.

Due to their flexibility and small size, the carbon nanotube fibers ofthe present disclosure can also follow the natural movement of a beatingheart without causing scarring or other inflammatory responses. In someembodiments, the carbon nanotube fibers of the present disclosure canalso be used to fabricate devices such as leads for implantablepacemakers, defibrillators, electrodes for electrocardiography (ECG),and conductive sutures for therapeutic purposes (e.g. treatment ofarrhythmias).

To Applicants' knowledge, the present disclosure also provides a firstexample of an additive process for restoring cardiac conduction and thefirst example of a conductive suture. By enabling improved conduction,the carbon nanotube fibers of the present disclosure can allow aparadigm shift in treatment of cardiac arrhythmias. For the first timeto Applicants' knowledge, Applicants can treat arrhythmias not byslowing or eliminating conduction (which often requires surgicaldestruction of cardiac tissue in a process called ablation or use ofmedications with multiple side effects and suboptimal efficacy), but byimproving conduction.

ADDITIONAL EMBODIMENTS

Reference will now be made to more specific embodiments of the presentdisclosure and experimental results that provide support for suchembodiments. However, Applicants note that the disclosure below is forillustrative purposes only and is not intended to limit the scope of theclaimed subject matter in any way.

Example 1 Pacing and Sensing Myocardial Activation and RestoringMyocardial Conduction Velocity with CNT Fibers

A series of experiments were performed on 4 sheep at the Texas HeartInstitute in full concordance with IACUC guidelines. Three sheep wereused to assess left ventricular (LV) conduction during LV pacing.Another sheep was used to assess right atrial (RA) conduction duringnon-paced, sinus rhythm. Myocardial conduction velocity was evaluated inall sheep.

The sheep were shaved, anesthetized, and intubated/ventilated. The vitalsigns of the sheep were monitored according to standard surgicalprocedures. A left lateral thoracotomy and a pericardial resection wereperformed to expose the epicardial surface of the heart. For the LVstudies, the LV was exposed and lifted with stay stitches.

As shown in FIG. 2A, decapolar catheters were sutured to the LVepicardial surface in a square between the epicardial arteries overlyingthe LV (5×5 cm). Thereafter, insulated CNT fibers were sewn into thecenter of the square of myocardium assayed as pacing leads.

In two LV studies, insulated CNT fibers were also sewn onto the LV apexand used to detect myocardial activation. In all experiments, thepolymer insulation was stripped from the CNT fibers at the point ofcontact with the tissue. Conduction times between the pacing wire andelectrodes were measured at cycle length (CL) of 400 ms. For the RAstudy, a linear lesion parallel to the tricuspid valve was created andno pacing was performed so that it could be possible to assess whetherCNT fibers can improve conduction during sinus (i.e., unpaced) heartrhythm.

To model anatomical conduction block, radiofrequency (RF) energy wasused to create a C-shaped transmural scar that would allow one area ofpaced wavefront to exit from the scar (4:30 o'clock position). RF energywas applied with a Safire™ Blu™ or Thermocool irrigated ablationcatheter (St. Jude Medical, St. Paul, Minn. and Biosense Webster,Diamond Bar, Calif., respectively) at 30-40 watts for a total of 5minutes. A scar-related increase in conduction time was confirmed byincremental ventricular pacing from baseline to cycle length of 400 ms.

In order to evaluate the effect of CNT fibers on conduction velocity,CNT fibers were sutured into the myocardium (FIG. 2A). The CNT fiberswere sewn across the scar at the 10:30 o'clock position, 180 degreesfrom the scar opening. After placement, the pacing protocol wasrepeated, and conduction times from the CNT pacing wires to eachelectrode were measured. The CNT fibers were then removed, and a silksuture was tested as a negative control. The silk suture was used as anegative control because silk is a carbon-based organic fiber withphysical and mechanical properties similar to those of CNT fiberswithout the conductivity of CNT fibers.

To determine whether sensed (non-paced currents) would also transferacross the wires, a fourth study was performed in which CNT fibers wereplaced in the RA. For this study, conduction delays and the changesassociated with CNT fiber use were measured in sinus rhythm, in theabsence of pacing. In addition to the epicardial electrode arrays,high-density epicardial activation mapping (60-80 points per condition)was performed in the last 2 studies (1 LV and 1 RA) by using the Carto 3(Biosense Webster, Diamond Bar, Calif.) mapping system (FIG. 5). Mappingwas conducted at baseline, after ablation, and after placement of theCNT fibers and silk control. Voltages and propagation/activationsequences were used to confirm alteration of the myocardial conductionvelocity.

Example 1.1 Results

The average conduction time during CNT pacing of the LV myocardialtissue was 21.47±1.15 ms in the 11 o'clock position for the 3 animalstested. Creating a C-shaped transmural scar on the LV myocardium with RFablation significantly increased conduction time across the scarred areain the 11 o'clock position (37.29±0.75 ms, FIG. 3A, p<0.001 versusbaseline). Introducing CNT fibers across the LV scar in the 11 o'clockposition significantly improved conduction time (26.35±0.89 ms, FIG. 3B,p<0.001 versus scar). Carto 3 imaging of the LV showed propagation ofthe wavefront through an isthmus overlaying the CNT fibers and boundedby the remaining scar tissue (FIG. 7). Placing a silk suture at the 11o'clock position did not improve conduction time across the scarredmyocardium (37.24±0.51 ms, FIG. 3A). This significant decrease inconduction time with CNT fibers compared to the RF scar condition wasmeasured in the entire area proximal to the CNT fiber implant (FIG. 4),but not in the locations away from it. These results indicate thatlongitudinal conduction across a scar can be facilitated by CNT fibersbut not by silk, an organic carbon-based fiber without the uniqueconductive properties of CNT fibers.

When the experiment was repeated in the RA using a linear scar between 2decapolar catheters, sinus rhythm (and not pacing) was improved when CNTfibers were placed across the scar (FIG. 6). This preliminary studysuggests that sinus rhythm alone may be sufficient to initiateconduction across CNT fibers.

In addition, when CNT fibers were used for LV pacing, the heart beatrate could be reliably controlled at the desired frequency throughoutthe entire experiment (FIG. 7A). Furthermore, optimal pacing thresholds(<0.2 mA) were obtained, even when pacing with a single CNT fiberfilament.

When CNT fibers were used as sensing electrodes, myocardial activationcould be reliably detected. Moreover, the average signal amplituderecorded after CNT fiber was introduced was two times higher than thatrecorded on the closest channel of the decapolar catheter (FIG. 7B).

These observations suggest a consistent and reliable electrical couplingbetween the CNT fibers and myocardial tissue. The observations alsosuggest that CNT fibers can be used to control and detect myocardialpotentials.

Without further elaboration, it is believed that one skilled in the artcan, using the description herein, utilize the present disclosure to itsfullest extent. The embodiments described herein are to be construed asillustrative and not as constraining the remainder of the disclosure inany way whatsoever. While the embodiments have been shown and described,many variations and modifications thereof can be made by one skilled inthe art without departing from the spirit and teachings of theinvention. Accordingly, the scope of protection is not limited by thedescription set out above, but is only limited by the claims, includingall equivalents of the subject matter of the claims. The disclosures ofall patents, patent applications and publications cited herein arehereby incorporated herein by reference, to the extent that they provideprocedural or other details consistent with and supplementary to thoseset forth herein.

What is claimed is:
 1. A method of improving electrical conductionacross an impaired region of a tissue, said method comprising: applyingan electrically conductive material across the impaired region of thetissue.
 2. The method of claim 1, wherein the tissue is selected fromthe group consisting of nerve tissue, muscle tissue, myocardial tissue,and combinations thereof.
 3. The method of claim 1, wherein the tissuecomprises myocardial tissue.
 4. The method of claim 1, wherein theimpaired region of the tissue comprises at least one of a scarred area,an ablated area, a bruised area, a cut area, a lesion, and combinationsthereof.
 5. The method of claim 1, wherein the impaired region of thetissue exhibits blocked or reduced electrical conduction.
 6. The methodof claim 1, wherein the impaired region of the tissue comprises impairedmyocardial tissue.
 7. The method of claim 1, wherein the applyingcomprises associating the electrically conductive material withnon-impaired regions of the tissue near the impaired region of thetissue.
 8. The method of claim 7, wherein the associating occurs bysuturing.
 9. The method of claim 7, wherein the non-impaired regions ofthe tissue are on opposite sides of the impaired region of the tissue.10. The method of claim 1, wherein the electrically conductive materialis selected from the group consisting of fibers, wires, metal wires,foils, metal foils, conductive polymers, carbon nanotubes, materialsmade from carbon nanotubes, and combinations thereof.
 11. The method ofclaim 1, wherein the electrically conductive material comprises fibers.12. The method of claim 1, wherein the electrically conductive materialcomprises diameters ranging from about 5 μm to about 500 μm.
 13. Themethod of claim 1, wherein the electrically conductive materialcomprises carbon nanotubes.
 14. The method of claim 13, wherein thecarbon nanotubes are selected from the group consisting of single-walledcarbon nanotubes, ultra-short single-walled carbon nanotubes,multi-walled carbon nanotubes, and combinations thereof.
 15. The methodof claim 1, wherein the electrically conductive material comprisescarbon nanotube fibers.
 16. The method of claim 15, wherein the carbonnanotube fibers are selected from the group consisting of single-walledcarbon nanotube fibers, multi-walled carbon nanotube fibers, alignedcarbon nanotubes fibers, and combinations thereof.
 17. The method ofclaim 1, wherein the electrically conductive material improves theelectrical conduction across the impaired region of the tissue byelectrically connecting non-impaired regions of the tissue near theimpaired region of the tissue.
 18. The method of claim 1, wherein theelectrically conductive material improves the electrical conductionacross the impaired region of the tissue by restoring or enhancingelectrical conduction across the impaired region of the tissue.
 19. Themethod of claim 1, wherein the electrically conductive material improvesthe electrical conduction across the impaired region of the tissue bydecreasing electrical current conduction time across the impaired regionof the tissue.
 20. A method of treating or preventing cardiac arrhythmiain a subject, said method comprising: applying an electricallyconductive material across an impaired region of a tissue in thesubject.
 21. The method of claim 20, wherein the applying comprisesassociating the electrically conductive material with non-impairedregions of the tissue near the impaired region of the tissue.
 22. Themethod of claim 21, wherein the associating occurs by suturing.
 23. Themethod of claim 21, wherein the non-impaired regions of the tissue areon opposite sides of the impaired region of the tissue.
 24. The methodof claim 20, wherein the electrically conductive material is selectedfrom the group consisting of fibers, wires, metal wires, foils, metalfoils, conductive polymers, carbon nanotubes, materials made from carbonnanotubes, and combinations thereof.
 25. The method of claim 20, whereinthe electrically conductive material comprises fibers.
 26. The method ofclaim 20, wherein the electrically conductive material comprisesdiameters that range from about 5 μm to about 500 μm.
 27. The method ofclaim 20, wherein the electrically conductive material comprises carbonnanotubes.
 28. The method of claim 27, wherein the carbon nanotubes areselected from the group consisting of single-walled carbon nanotubes,ultra-short single-walled carbon nanotubes, multi-walled carbonnanotubes, and combinations thereof.
 29. The method of claim 20, whereinthe electrically conductive material comprises carbon nanotube fibers.30. The method of claim 29, wherein the carbon nanotube fibers areselected from the group consisting of single-walled carbon nanotubefibers, multi-walled carbon nanotube fibers, aligned carbon nanotubesfibers, and combinations thereof.
 31. The method of claim 20, whereinthe tissue comprises myocardial tissue.
 32. The method of claim 20,wherein the impaired region of the tissue comprises at least one of ascarred area, an ablated area, a bruised area, a cut area, a lesion, andcombinations thereof.
 33. The method of claim 20, wherein the impairedregion of the tissue exhibits blocked or reduced electrical conduction.34. The method of claim 20, wherein the impaired region of the tissuecomprises impaired myocardial tissue.
 35. The method of claim 20,wherein the electrically conductive material improves the electricalconduction across the impaired region of the tissue by electricallyconnecting non-impaired regions of the tissue near the impaired regionof the tissue.
 36. The method of claim 20, wherein the electricallyconductive material improves the electrical conduction across theimpaired region of the tissue by restoring or enhancing electricalconduction across the impaired region of the tissue.
 37. The method ofclaim 20, wherein the electrically conductive material improves theelectrical conduction across the impaired region of the tissue bydecreasing electrical current conduction time across the impaired regionof the tissue.
 38. The method of claim 20, wherein the subject is ahuman being.
 39. The method of claim 20, wherein the cardiac arrhythmiais ventricular arrhythmia.
 40. A method of transmitting electricalsignals to a tissue, said method comprising: associating the tissue withan electrical wiring, wherein the electrical wiring comprises carbonnanotubes; and transmitting electrical signals to the tissue through theelectrical wiring.
 41. The method of claim 40, wherein the associatingcomprises directly associating the electrical wiring with the tissue.42. The method of claim 40, wherein the associating comprises indirectlyassociating the electrical wiring with the tissue.
 43. The method ofclaim 40, wherein the associating comprises implanting the electricalwiring into the tissue.
 44. The method of claim 40, wherein theassociating comprises suturing the electrical wiring into the tissue.45. The method of claim 40, wherein the associating comprises adheringthe electrical wiring to the tissue.
 46. The method of claim 40, whereinthe carbon nanotubes are selected from the group consisting ofsingle-walled carbon nanotubes, ultra-short single-walled carbonnanotubes, multi-walled carbon nanotubes, and combinations thereof. 47.The method of claim 40, wherein the carbon nanotubes are in the form ofcarbon nanotube fibers.
 48. The method of claim 47, wherein the carbonnanotube fibers are selected from the group consisting of single-walledcarbon nanotube fibers, multi-walled carbon nanotube fibers, alignedcarbon nanotubes fibers, and combinations thereof.
 49. The method ofclaim 40, wherein the electrical wiring comprises a conductive elementand a point of attachment.
 50. The method of claim 49, wherein theconductive element comprises carbon nanotube fibers.
 51. The method ofclaim 50, wherein the point of attachment comprises carbon nanotubefibers.
 52. The method of claim 50, wherein the point of attachment isin the form of an electrode.
 53. The method of claim 50, wherein theelectrical wiring comprises a plurality of points of attachment.
 54. Themethod of claim 40, wherein the transmittal of electrical signals to thetissue comprises delivery of an electrical signal from an electricaldevice associated with the electrical wiring.
 55. The method of claim54, wherein the electrical device is selected from the group consistingof medical devices, pacemakers, defibrillators, and combinationsthereof.
 56. The method of claim 40, wherein the tissue is selected fromthe group consisting of nerve tissue, muscle tissue, myocardial tissue,and combinations thereof.
 57. The method of claim 40, wherein the tissuecomprises myocardial tissue.
 58. The method of claim 40, wherein thetissue is an isolated tissue.
 59. The method of claim 40, wherein thetissue is part of a subject.
 60. The method of claim 40, wherein thetissue comprises myocardial tissue in a subject, and wherein the methodis used for cardiac resynchronization in the subject.
 61. The method ofclaim 40, wherein the tissue comprises myocardial tissue in a subject,and wherein the method is used for defibrillation in the subject.
 62. Amethod of sensing electrical signals from a tissue, said methodcomprising: associating the tissue with an electrical wiring, whereinthe electrical wiring comprises carbon nanotubes; and sensing electricalsignals from the tissue through the electrical wiring.
 63. The method ofclaim 62, wherein the associating comprises directly associating theelectrical wiring with the tissue.
 64. The method of claim 62, whereinthe associating comprises indirectly associating the electrical wiringwith the tissue.
 65. The method of claim 62, wherein the associatingcomprises implanting the electrical wiring into the tissue.
 66. Themethod of claim 62, wherein the associating comprises suturing theelectrical wiring into the tissue.
 67. The method of claim 62, whereinthe associating comprises adhering the electrical wiring to the tissue.68. The method of claim 62, wherein the carbon nanotubes are selectedfrom the group consisting of single-walled carbon nanotubes, ultra-shortsingle-walled carbon nanotubes, multi-walled carbon nanotubes, andcombinations thereof.
 69. The method of claim 62, wherein the carbonnanotubes are in the form of carbon nanotube fibers.
 70. The method ofclaim 69, wherein the carbon nanotube fibers are selected from the groupconsisting of single-walled carbon nanotube fibers, multi-walled carbonnanotube fibers, aligned carbon nanotubes fibers, and combinationsthereof.
 71. The method of claim 62, wherein the electrical wiringcomprises a conductive element and a point of attachment.
 72. The methodof claim 71, wherein the conductive element comprises carbon nanotubefibers.
 73. The method of claim 72, wherein the point of attachmentcomprises carbon nanotube fibers.
 74. The method of claim 72, whereinthe point of attachment is in the form of an electrode.
 75. The methodof claim 71, wherein the electrical wiring comprises a plurality ofpoints of attachment.
 76. The method of claim 62, wherein the sensing ofelectrical signals from the tissue comprises sensing the electricalsignals in an electrical device associated with the electrical wiring.77. The method of claim 76, wherein the electrical device is selectedfrom the group consisting of medical devices, pacemakers,defibrillators, electrocardiographs, and combinations thereof.
 78. Themethod of claim 62, wherein the tissue is selected from the groupconsisting of nerve tissue, muscle tissue, myocardial tissue, andcombinations thereof.
 79. The method of claim 62, wherein the tissuecomprises myocardial tissue.
 80. The method of claim 62, wherein thetissue is an isolated tissue.
 81. The method of claim 62, wherein thetissue is part of a subject.
 82. The method of claim 62, wherein thetissue comprises myocardial tissue in a subject, and wherein the sensingof electrical signals from the myocardial tissue comprises sensing ofcardiac electrical activity.
 83. An electrical wiring for sensing ortransmitting electrical signals, wherein the electrical wiring comprisescarbon nanotubes.
 84. The electrical wiring of claim 83, wherein theelectrical wiring consists essentially of carbon nanotubes.
 85. Theelectrical wiring of claim 83, wherein the electrical wiring comprises aconductive element and a point of attachment.
 86. The electrical wiringof claim 85, wherein the conductive element comprises carbon nanotubefibers.
 87. The electrical wiring of claim 85, wherein the point ofattachment comprises carbon nanotube fibers.
 88. The electrical wiringof claim 85, wherein the point of attachment is in the form of anelectrode.
 89. The electrical wiring of claim 85, wherein the electricalwiring comprises a plurality of points of attachment.
 90. The electricalwiring of claim 83, wherein the carbon nanotubes are selected from thegroup consisting of single-walled carbon nanotubes, ultra-shortsingle-walled carbon nanotubes, multi-walled carbon nanotubes, andcombinations thereof.
 91. The electrical wiring of claim 83, wherein thecarbon nanotubes are in the form of carbon nanotube fibers.
 92. Theelectrical wiring of claim 91, wherein the carbon nanotube fibers areselected from the group consisting of single-walled carbon nanotubefibers, multi-walled carbon nanotube fibers, aligned carbon nanotubesfibers, and combinations thereof.
 93. The electrical wiring of claim 83,wherein the electrical wiring is associated with an electrical device,wherein the electrical device is selected from the group consisting ofmedical devices, pacemakers, defibrillators, electrocardiographs, andcombinations thereof.
 94. A suture thread comprising carbon nanotubes.95. The suture thread of claim 94, wherein the carbon nanotubes are inthe form of carbon nanotube fibers.
 96. The suture thread of claim 95,wherein the carbon nanotube fibers are selected from the groupconsisting of single-walled carbon nanotube fibers, multi-walled carbonnanotube fibers, aligned carbon nanotubes fibers, and combinationsthereof.
 97. The suture thread of claim 95, wherein the suture threadconsists essentially of carbon nanotube fibers.
 98. The suture thread ofclaim 94, wherein the suture thread comprises diameters that range fromabout 5 μm to about 500 μm.